Drug permeability screening assays are known, in the prior art. With reference to FIG. 1, a typical arrangement for conducting such assays is depicted. A multiwell insert plate 10 is shown having a plurality of open wells 12 with a porous membrane or filter 14 extending across a bottom end of each of the wells 12. The filter 14 is typically of polyvinylidene difluoride (PVDF), polyethylene terephthalate (PET) or a polycarbonate (PC) material. A corresponding receiver plate 16 is also shown having closed-bottom receiver wells 18. In use, buffered solutions containing compounds to be analyzed are disposed into the receiver wells 18. Buffered solutions without the compounds of interest are disposed into the wells 12 of the insert plate 10, and the insert plate 10 is placed atop the receiver plate 16 with the filters 14 coming into contact with the buffered solutions of compounds contained in the receiver wells 18. The concentrations of the compounds in the solutions of both the insert plate 10 and the receiver plate 16 are analyzed to observe the diffusion of the compounds through the filters 14 and to determine the compounds' permeabilities.
Under certain circurmstances (e.g., certain assays), it may be desirable to have one or more cell monolayers formed on the filters. With reference to FIG. 2, it is known in the art to dispose a cell media solution into the wells 12 of the insert plate to incubate cells on the respective interior surfaces of the filters 14 and to form cell monolayers thereon. However, greater difficulty exists in forming cell monolayers on the exterior surfaces of the filters. As shown in FIG. 3, a technique has been developed where the insert plate 10 is inverted and a drop of cell media solution is disposed onto each of the filters 14. Because a limited volume of the cell media may be disposed onto each of the filters 14, it is difficult to consistently achieve a tight cell monolayer, which requires high cell density and long incubation time. The failure to form a tight cell monolayer may lead to “holes” in the cell monolayer and possible failure in the drug permeability screening assays.
Formation of cell monolayers on the exterior surfaces of the filter membranes is desired for several reasons. First with cell monolayers on both sides of the filter membranes, particularly of different types of cells, cell communications can be studied. Second, the exterior surface monolayers permit researchers to conduct polarized drug transport studies in a manner which permits the use of identical buffer solution configurations for each direction of drug transport (apical to basolateral and basolateral to apical).